The long-term goal of this study is to understand the molecular, biochemical, and immunologic factors that contribute to the pathogenesis of Enterococcus faecalis and Enterococcus faecium infections. The understanding of the interaction between bacteria and the human host defense system will be the basis for the development of new means of preventing otherwise untreatable enterococcal infections. The studies will provide new and clinically useful information because it has not previously been appreciated that enterococci possess a capsule which could be used as a vaccine antigen. The development of a serotyping system for enterococci will be the necessary basis for the application of these antigens to immunotherapy and immunoprophylaxis regimens. The molecular studies will focus on the role of capsular polysaccharides of enterococci in pathogenesis, using animal models relevant to important human enterococcal infections, and the genetic mechanisms involved in capsule production. The immunologic studies will focus on determining whether the isolated antigens are targets for protective immune responses. At the end of these studies, we expect to have a better understanding of the immunology of capsular polysaccharides of enterococci, a definition of their role in the pathogenesis of specific enterococcal infections, and their potential for the development of immunotherapies to prevent and/or treat infection in hospital patients.